Prospective Studies on the Risk of Rheumatoid Arthritis: The European Risk RA Registry

Abstract

Background: The accumulation of risk for the development of rheumatoid arthritis (RA) is regarded as a continuum that may start with interacting environmental and genetic factors, proceed with the initiation of autoimmunity, and result in the formation of autoantibodies such as anti-citrullinated peptide antibodies (ACPA). In parallel, at-risk individuals may be asymptomatic or experience joint pain (arthralgia) that is itself non-specific or clinically suspicious for evolving RA, even in the absence of overt arthritis. Optimal strategies for the management of people at-risk of RA, both for symptom control and to delay or prevent progression to classifiable disease, remain poorly understood.

Methods: To help address this, groups of stakeholders from academia, clinical rheumatology, industry and patient research partners have collaborated to advance understanding, define and study different phases of the at-risk state. In this current report we describe different European initiatives in the field and the successful effort to build a European Registry of at-risk people to facilitate observational and interventional research.

Results: We outline similarities and differences between cohorts of at-risk individuals at institutions spanning several countries, and how to best combine them within the new database. Over the past 2 years, besides building the technical infrastructure, we have agreed on a core set of variables that all partners should strive to collect for harmonization purposes.

Conclusion: We emphasize to address this process from different angles and touch on the biologic, epidemiologic, analytic, and regulatory aspects of collaborative studies within a meta-database of people at-risk of RA.

Keywords: database; multi-center study; observational; prevention; rheumatoid arthritis.

Figure 1

Visualizing the development of RA and key aims in future healthcare management of people in different stages/phenotypes at-risk of developing arthritis/RA.

Figure 2

Overview of study time points in the at-risk programs, following up antibody (CCP and/or RF) positive and negative individuals until occurrence of arthritis detected by imaging (KI) or clinically (MUV, UKER, LUMC, UNEW), potentially with overlap to classification as RA according to the 2010 ACR/EULAR criteria.